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Toxicological information

Toxicity to reproduction: other studies

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Administrative data

Endpoint:
toxicity to reproduction: other studies
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
5 December - 19 December 1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well performed guideline study with some deviations from guideline.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
other: OECD Guidelines 414 and 421
Deviations:
yes
Remarks:
two dose groups, 3 days recovery period
GLP compliance:
yes
Type of method:
in vivo

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Purity: 99.8%

Test animals

Species:
rat
Strain:
other: Hoe: WISKf (SPF 71)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hoechst AG, Pharma Forschung Toxikologie
- Age at study initiation: males 6-7 weeks; females 10-11 weeks (pregnant)
- Weight at study initiation: males 165-176 g, females 187-231 g
- Housing: single in Makrolon type-3 cages with wire mesh tops and standard softwood bedding
- Diet (e.g. ad libitum): Altromin R 1324 pellets ad libitum
- Water (e.g. ad libitum): Community tap water ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2 °C
- Humidity (%): 50 +/- 20 %
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 5.12.1983 To: 19.12.1983

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure (if applicable):
whole body
Vehicle:
other: Air
Details on exposure:
Exposure period: 14 days
Recovery period: 3 days
Control group: None
Method: OECD 412 (OECD 1981)
5 males and 5 pregnant females (rat) were used per group (whole body exposure).
Ethylene glycol dimethyl ether was applied to a vaporizer and continuously evaporated at 80°C. The resulting test substance/air mixture was carried to the inhalation chambers using an air stream of 800 L/h. The Ethylene glycol dimethyl ether concentration was determined by a Miran 80 photometer every 15 min. CO, CO2 (Uras 2 T Infrared-Gasanalysator) and O2 (Magnos 3 magnetic Oxygen-Analysator) concentration as well as humidity (Transmitter HMT 12) and temperature (CMR-Meßumformer TEU 320) were determined continuously.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Please refer to "Details on inhalation exposure"
Duration of treatment / exposure:
6 hours/d
Frequency of treatment:
5 days/week
Duration of test:
14 days
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
100 ppm (0.374 mg/L)
Basis:
analytical conc.
Remarks:
Doses / Concentrations:
500 ppm (1.87 mg/L)
Basis:
analytical conc.
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Animals were observed for mortality and clinical symptoms once before each exposure, several times during exposure, once after each exposure and daily during the recovery period. Body weights were recorded before treatment (females) and weekly during the study (females), food consumption was determined weekly. Haematological examination (haemoglobin concentration, reticulocyte count, haematocrit, erythrocyte count, leucocyte count, thrombocyte count, differential blood count and clotting time) was performed in females 3 days before the first exposure and 3 days after the last exposure. The rats were sacrificed 3 days (21 days post copulationem) after the last treatment, and examined for gross macroscopical changes. Foetuses were removed by Caesarean section. Testes and epidymis of the treated male rats were examined histopathologically.
Statistics:
no data

Results and discussion

Effect levels

Dose descriptor:
NOAEC
Effect level:
< 0.374 mg/L air (analytical)
Sex:
male
Basis for effect level:
other: Oligospermia

Observed effects

Mortality/Viability:
All animals survived and no clinical signs were noted at 100 ppm. No deaths or clinical signs occurred in the rats of the 500 ppm dose group.

Body weight:
Body weight gain of the rats at 100 ppm exposure was unaffected. The body weight of the male rats of the 500 ppm dose group was unaffected; the body weight of three female rats was decreased.

Food consumption:
There were no effects upon the mean daily food consumption observed in the 100 ppm dose group. Food consumption of all females in the 500 ppm dose group was decreased.

Haematology:
There were no changes noted at 100 ppm. At 500 ppm the leucocyte count was decreased in all animals.

Macroscopic/microscopic findings:
No changes occurred all rats. The microsopic examination of the testes and epidymis showed oligospermia at 100 ppm and severe lesions of the seminiferous epithelium at 500 ppm exposure.

Maternal/developmental toxicity:
At 100 ppm retardation of foetal development was observed. At 500 ppm an increase of resorptions occurred.

Applicant's summary and conclusion

Conclusions:
Based on the observed oligospermia in rats and the retardation of foetal development and resorption of embryos in rats, the NOAEC is considered to be lower than 100 ppm (0.374 mg/L).
Executive summary:

A 14 day inhalation toxicity study was performed in rats. The animals were exposed to an Ethylene glycol dimethyl ether atmosphere of 100 ppm (0.374 mg/L) and 1000 ppm (1.87 mg/L). All animals survived and no clinical signs were noted at 100 ppm. No deaths or clinical signs occurred in the rats of the 500 ppm dose group. Body weight gain of the rats at 100 ppm exposure was unaffected. The body weight of the male rats of the 500 ppm dose group was unaffected; the body weight of three female rats was decreased. There were no effects upon the mean daily food consumption observed in the 100 ppm dose group. Food consumption of all females in the 500 ppm dose group was decreased. There were no changes in haematology noted at 100 ppm. At 500 ppm the leucocyte count was decreased in all animals. No macroscopic changes occurred in all rats. The microsopic examination of the testes and epidymis showed oligospermia at 100 ppm and severe lesions of the seminiferous epithelium at 500 ppm exposure. At 100 ppm retardation of foetal development was observed. At 500 ppm an increase of resorptions occurred.